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Plasma Cell Disorders
Performance analysis of AL amyloidosis cardiac biomarker staging systems with special focus on renal failure and
atrial arrhythmia
Ferrata Storti Foundation
Haematologica 2019 Volume 104(7):1451-1459
Selected contents of this manuscript were presented during the XVIth International Symposium on Amyloidosis in Kumamoto, Japan (oral presentation on 28th March 2018, OP48).
Tobias Dittrich,1,2,3 Axel Benner,4 Christoph Kimmich,1,2 Fabian aus dem Siepen,2,5 Kaya Veelken,1,2 Arnt V. Kristen,2,5 Tilmann Bochtler,1,2,3 Hugo A. Katus,5 Carsten Müller-Tidow,1,2 Ute Hegenbart1,2 and Stefan O. Schönland1,2
1Department of Internal Medicine V, Division of Hematology/Oncology, Heidelberg University Hospital; 2Amyloidosis Center, Heidelberg University Hospital; 3Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, Heidelberg University Hospital; 4Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg and 5Department of Internal Medicine III, Division of Cardiology, Heidelberg University Hospital, Germany
ABSTRACT
Systemic light chain amyloidosis is a rare and life-threatening disorder, for which accurate risk stratification is crucial. Current cardiac staging systems (MAYO2004, MAYO3b, and MAYO2012) are mainly based on biomarkers, which have uncertain reliability in the context of atrial fib- rillation, arrhythmia or pacemaker stimulation as well as renal insufficiency. We compared the performance of the established staging systems with par- ticular regard to these comorbidities in 1,224 patients with systemic light chain amyloidosis diagnosed at our center from July 2002 until March 2017. We first characterized the subsets with an estimated glomerular filtration rate <50 mL/min/1.73 m2 (415 patients) and any kind of atrial arrhythmia (183 patients) as unique high-risk subgroups with similarly increased car- diac biomarkers (χ2-test, all P<0.001). This resulted in a shift towards higher risk stages and reduced median overall survival compared to those of patients with better kidney function or without atrial arrhythmia in univari- ate analyses (13 vs. 46 months and 17 vs. 53 months, respectively; both P<0.001). Performance analysis revealed that predictions in the entire cohort were least precise with the MAYO2004 staging system and most precise with the MAYO3b system. This performance pattern was almost preserved for patients with an estimated glomerular filtration rate <50 mL/min/1.73 m2, but less so for those with atrial arrhythmias. The MAYO3b staging system was most robust. Importantly, atrial arrhythmia retained its prognostic value in multivariable analysis including age, differ- ence between involved and uninvolved free light chains, and any staging system, while estimated glomerular filtration rate <50 mL/min/1.73 m2 was not statistically significant in multivariable analysis with the MAYO3b stag- ing system. In conclusion, our results favor the MAYO3b staging system due to its consistently best performance and retained applicability in the subgroups with atrial arrhythmia and estimated glomerular filtration rate <50 mL/min/1.73 m2.
Introduction
Systemic light chain amyloidosis (AL) is a life-threatening protein deposition disorder with an annual incidence in the western world of about 8-12 cases per one million inhabitants.1 The disease is initiated by clonal plasma cells in the bone marrow,2 which secrete the amyloid-precursor proteins: free light chains (FLC) with a propensity to misfold and aggregate. In the fatal course of this dis- ease, excessive amyloid causes dysfunction of vital organs such as the heart, kid- neys or liver, which results in substantial morbidity and mortality.1,3
Correspondence:
STEFAN O. SCHÖNLAND
stefan.schoenland@med.uni-heidelberg.de
UTE HEGENBART
ute.hegenbart@med.uni-heidelberg.de
Received: August 26, 2018. Accepted: January 15, 2019. Pre-published: January 17, 2019.
doi:10.3324/haematol.2018.205336
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/7/1451
©2019 Ferrata Storti Foundation
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haematologica | 2019; 104(7)
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